HIV infection induces lymph node fibrosis and persistent inflammation even during successful ART. Telmisartan, an angiotensin II receptor blocker, could prevent fibrosis and inflammation in individuals with HIV when administered at time of ART initiation in acute HIV infection (AHI). We assessed telmisartan effect on preventing HIV-mediated damage and on HIV reservoirs in tissues in people randomized during AHI to telmisartan+ART (T+ART) versus ART alone.
Cryopreserved LN cells at time of AHI and 48 weeks after were included from RV408 participants randomized to T+ART (n=7) versus ART alone (n=4). Additionally, LN samples from other RV254 participants at AHI (n=26) and post-ART at wk48 (n=13), to compare the RV408 randomized group to a larger group. Nine uninfected individuals were also included. B cells, CD4 and CD8 T cells were characterized by flow cytometry when sufficient cells permitted. Total HIV DNA levels in CD4 T cells were quantified by ultrasensitive PCR; collagen, TGFβ and TNFα were measured by immunohistochemistry.
In AHI, no differences were observed between the groups. At wk48, in LN, the frequencies of resting memory (RM) B cells (CD21+CD27+IgG+CD20+) were decreased in ART group in the RV408 and RV254 but maintained at similar levels as controls in the T+ART group (Fig.1a). Conversely, frequencies of tissue-like memory B cells and intermediate memory B cells were lower in LN in the T+ART group compared to the RV408 ART group (p=0.015 and p=0.039, respectively) as well as the RV254 group. In addition, in LN, frequencies of regulatory B cells (CD38hiCD24hiCD19+) were higher in the T+ART group compared to uninfected controls and trending to be higher compared to the ART groups (Fig.1b). No difference was observed between the two groups in activated CD4 and CD8 T cells (CD38+HLA-DR+ and Ki67+Bcl-2lo) in LN. The LN HIV DNA levels were not different between the T+ART and the ART groups (Fig.1c). No differences were observed in collagen deposition, TGFβ and TNFα between the two RV408 groups.
Although the number of studied samples in the T+ART group in our study limits definitive conclusions, addition of telmisartan to ART during AHI did not reduce T cell activation, HIV reservoir or collagen deposition in LN. However, we observed higher RM B cells and Bregs in LN after T+ART versus ART alone. These data suggest that adjunctive therapy in AHI with telmisartan over 48 weeks may preserve immune cells in LN especially the B cell compartment.